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Genetically\u2010determined or acquired dysregulation of the complement is frequently identified in patients with aHUS, pregnancy\u2010related hemolytic uremic syndrome (HUS), and severe hypertension\u2010associated HUS. In contrast, it is still unclear whether self\u2010limited complement activation, which frequently occurs in other forms of HUS, provides key mechanistic clues or results from endothelial damage. Development of novel biomarkers is underway to firmly establish complement\u2010driven pathogenesis. C5 blockade therapy has revolutionized the management of aHUS patients, resulting in a halving of the subpopulation under chronic dialysis over the course of a few years. On the other hand, the efficacy of C5 blockade in secondary forms of HUS, as assessed by small and uncontrolled case series, is less compelling and should be investigated through properly designed prospective clinical trials. The increased risk of meningococcal infection, related to C5 inhibition, must be rigorously addressed with suitable prophylaxis. Treatment duration should be determined based on an individualized benefit\/risk assessment.<\/jats:p>","DOI":"10.1002\/ajh.26854","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:58:33Z","timestamp":1674435513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Complement\u2010driven hemolytic uremic syndrome"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5314-8154","authenticated-orcid":false,"given":"Juliette","family":"Leon","sequence":"first","affiliation":[{"name":"Department of Kidney and Metabolic Diseases Transplantation and Clinical Immunology, Necker Hospital, AP\u2010HP  Paris France"},{"name":"Universit\u00e9 Paris\u2010Cit\u00e9  Paris France"},{"name":"Inserm UMR_S1163, IHU IMAGINE  Paris France"},{"name":"Centre of Expertise for the French Nationwide TMA Network (CNR\u2010MAT)  Paris 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